Previous studies have shown that roles of Toll-like receptor 2 (TLR2) in mammalian brain encompass its involvement in neuroinflammation and neurodevelopmental processes such as proliferation and differentiation of neuronal progenitor cells. The aim of this study was to determine whether lack of TLR2 influences on the expression of proteins which participate in synaptic plasticity (neuroplastin) and membrane ion transport (P-type ATPases) in mouse brain. The variations of the synaptic proteome, gene and protein expression of neuroplastin and P-type ATPases as well as their tissue and membrane localization, ATPases catalytic activity, and gangliosidome were analyzed in the tissue samples of cortex, hippocampus, and cerebellum derived from mouse model lacking TLR2 in comparison to control tissue. Results demonstrate that the lack of TLR2 is associated with: a) adjustments in the synaptic proteome related markedly to protein systems involved in regulation of axon projections and myelinization, glutamatergic transmission, and energy metabolism; b) lower expression of neuroplastin in the hippocampus and cerebellum indicating potential loss of synapses, while detected variable content of P-type ATPases may suggest reduced number of synapses in the hippocampus and increased number of astrocytes in the cerebellum; c) higher expression and increased catalytic activity of plasma membrane calcium ATPase in hippocampus arguing for deranged calcium transport; d) increased ratio of simple ganglioside specie GD3 in the hippocampus and complex gangliosides GT1b and GQ1b in the cerebellum which may reflect alteration of membrane homeostasis and specific membrane functions such as proliferation and ion transport. In conclusion, presented findings reveal that the lack of TLR2 in mouse brain effects on the expression and function of membrane systems essential for synaptic plasticity and ion transport, opening new avenues for investigation of yet undescribed roles of TLR2 in the mammalian brain.